Defined criteria for eltrombopag initiation and discontinuation were lacking and were determined by the medical course

Defined criteria for eltrombopag initiation and discontinuation were lacking and were determined by the medical course. prognosis remains poor with a high mortality rate due to GVHD, illness and/or bleeding, especially in individuals with main engraftment failure. Recent and data showed that stimulation of the c-MPL-signalling pathway by thrombopoietin (TPO) agonists may have a significant influence on maintenance and self-renewal of HSCs.7C10 Recovery of trilineage haematopoiesis after eltrombopag treatment was highly effective in patients with severe aplastic anaemia (SAA) and led to US Food and Drug Administration approval for treatment of SAA, immune thrombocytopenia and hepatitis-C-related thrombocytopenia.11C15 In the establishing of HSCT, several authors investigated retrospectively the part of eltrombopag in refractory thrombocytopenia after allogeneic HSCT and reported encouraging effects with significant platelet recovery until achieving transfusion independence.16C19 On the basis of these effects current phase II tests using TPO agonists for long term thrombocytopenia after HSCT have been initiated, (“type”:”clinical-trial”,”attrs”:”text”:”NCT01791101″,”term_id”:”NCT01791101″NCT01791101, “type”:”clinical-trial”,”attrs”:”text”:”NCT01000051″,”term_id”:”NCT01000051″NCT01000051, “type”:”clinical-trial”,”attrs”:”text”:”NCT01927731″,”term_id”:”NCT01927731″NCT01927731). Further, studies have shown that TPO promotes actually multilineage haematopoiesis and raises peripheral human being platelets and white blood cell counts by recruiting and expanding HSC/haematopoietic progenitor cells from your bone marrow compartment of a NOD/SCID xenotransplant model.20,21 These observations led to the hypothesis that eltrombopag may have a role in haematopoietic recovery in sole, bi- and even trilineage cytopenias in individuals after allogeneic HSCT as recently reported.22C24 In the present analysis we statement a single centre encounter with eltrombopag in post-allogeneic transplant individuals with refractory single and multilineage cytopenias due to poor graft function or primary engraftment failure. Patients and methods Between January 2015 and August 2018 a total of 216 individuals underwent allogeneic HSCT in the Stem Cell Transplant Center, AOU Amotl1 Citt della Salute e della Scienza in Turin, Italy. Overall, 12 (5.5%) individuals developed refractory single or multilineage cytopenias after transplant due to graft failure (sponsor disease; Haplo, haploidentical donor; HSCT, haematopoietic stem cell transplant; Mac WAY-100635 Maleate pc, myeloablative conditioning; MDS, myelodysplastic syndrome; MMF, mycophenolate mofetil; MPAL, mixed-phenotype acute leukaemia; MSD, matched sibling donor; MTX, methotrexate; MUD, matched unrelated donor; neg, bad; NR, not reported; PBSC, peripheral blood stem cells; PLT, platelets; pos, positive; PT/CY, post-transplant cyclophosphamide; R, recipient; RIC, reduced intensity conditioning; TNC, total nuclear WAY-100635 Maleate cells. A total of 11 individuals accomplished neutrophil recovery 500??106/L after a median of 20.5 (range: 15C33) days and 8 patients achieved platelets 20.000??106/L after a median of 20.5 (range: 13C37) days after transplant. Cytopenias and treatment characteristics Cytopenias and treatment WAY-100635 Maleate characteristics are summarised in Table 2. Six individuals developed main poor graft function while in five individuals poor graft function was secondary to GVHD (77,000 (range: 50,000C218,000)??106/L after eltrombopag treatment, 2325 (range: 0C4260)??106/L after a median of 200 (21C379) days, 129 (74C154) g/L (2325 (0C4260)??106/L (could previously even demonstrate that eltrombopag induces in umbilical cord blood transplants multilineage responses through the expansion of bone marrow HSCs and haematopoietic progenitor cells.21 On the basis of these results, the activation of residual HSCs by TPO agonists was postulated and attempted by using eltrombopag in the setting of persistent cytopenia after HSCT by several organizations with promising results. Tang using eltrombopag as first-line treatment in individuals with main engraftment failure and poor graft function (as well as in the study of Tang showed that in individuals with aplastic anaemia a T-cell clone markedly inhibited the growth of haematopoietic progenitor cells by direct cellCcell contact and IFN-gamma secretion in response to CD34+cells.29 They hypothesised that these cytotoxic T cells may even contribute to the pathogenesis of aplastic anaemia.29 Further, iron overload has been shown to have a suppressive effect on the erythroblast differentiation of human CD34+ cells. It increases the level of the intracellular reactive oxygen species (ROS) advertising apoptosis of immature erythroblasts by suppressing BCL2 gene manifestation.30,31 Kong explained a patient with severe aplastic anaemia who was diagnosed with poor graft function after transplantation and achieved total haematopoietic recovery mainly due to iron-chelation therapy.35 In the present study the median ferritin level before eltrombopag treatment initiation was 3126 (range: 897C6770) ng/ml with 9/12 individuals possessing a ferritin level 2000?ng/ml. This may be attributed to significant blood transfusion support as nearly all were individuals with acute leukaemia. Iron chelation was performed in six out of nine individuals with severe anaemia, and all except one (no. 10) became blood transfusion self-employed. On the basis of this initial result, a synergistic effect between eltrombopag and iron-chelation therapy may be hypothesised. At time of last follow up, three individuals were lifeless and one with main engraftment failure was successfully retransplanted. Of the remaining eight individuals seven managed CR criteria and are transfusion self-employed. Our study offers several limiting factors, namely the retrospective character, the.